key: cord-277611-3iynrfzq
authors: Buetti, Niccolò; Patrier, Juliette; Le Hingrat, Quentin; Loiodice, Ambre; Bouadma, Lila; Visseaux, Benoit; Timsit, Jean-François
title: Risk factors for SARS-CoV-2 detection in blood of critically ill patients
date: 2020-09-02
journal: Clin Infect Dis
DOI: 10.1093/cid/ciaa1315
sha: 
doc_id: 277611
cord_uid: 3iynrfzq

nan

M a n u s c r i p t 2 Dear Editor, Data on detection of SARS-CoV-2 viral RNA within COVID-19 patients' blood are scarce [1] [2] [3] . The recently published article by Veyer et al. described plasma SARS-CoV-2 viral load in 58 noncritically and critically ill patients [4] . In their multivariate analysis the authors showed that SARS-CoV-2 RNAaemia was strongly associated with the clinical class, with higher level RNAaemia among critically ill patients. However, to date, risk factors for detectable SARS-CoV-2 RNAaemia in critically ill patients remain unknown. Therefore, we conducted a similar study using prospectively collected data at the Bichat University Hospital, France, in order to identify risk factors for SARS-CoV-2 detection in blood in critically ill intubated patients. All included patients had a SARS-CoV-2 positive nasopharyngeal swab before intensive care (ICU) admission. During the ICU stay, all patients underwent a regularly monitoring of SARS-CoV-2 RNAaemia. All blood specimens were sent to the virology laboratory and used for RNA extraction, using MagnaPure Large Volume Total NA kit (Roche), and amplification by real time polymerase chain reaction (RT-PCR) techniques using RealStar SARS-CoV-2 RT-PCR RUO assay (Altona). Of note, such RT-PCR assay presents a low limit of detection at 625 copies/mL [5] , probably slightly higher than droplet PCR assay used by Veber et al. In order to identify risk factors for SARS-CoV-2 detection in blood, we used univariable and multivariable mixed-effect logistic models for clustered data (PROC GLIMMIX of SAS) and we adjusted for the time between symptoms' onset and date of sampling. This model takes into account the clustering effect of multiple sampling per patient.

From March to April 2020, in 42 patients 81 blood samples for SARS-CoV-2 detection were collected; 30 samples (37%) were positive. Thirty-four (81%) patients were male and the median age was 58 (IQR: 46; 67); 22 (52%) had a cardiovascular comorbidity and eight (19%) were immunosuppressed. Twenty-two (52%) and 18 (43%) patients received corticosteroids and lopinavir/ritonavir. The median time to negativity (i.e., time between onset of symptoms and viral clearance process from blood) was 17 days (IQR: 12; 21). Using univariable mixed-effect models after adjusting for the time interval between onset of symptoms and date of sampling, we showed that immunosuppression (OR 12.16, 95% CI 1.74-84.93, p=0.013) and chronic renal failure (OR 5.98, A c c e p t e d M a n u s c r i p t 3 95% CI 1.14-31.35, p=0.035) increased the risk for SARS-CoV-2 detection in blood (Table) .

Interestingly, SARS-CoV-2 detection in blood was not associated with 6-week mortality. In the multivariable analysis, immunosuppression significantly increased the risk for SARS-CoV-2 detection in blood (OR 8.95, 95% CI 1.17; 68.38, p=0.035, Table) .

Veyer et al. showed that SARS-CoV-2 RNAaemia was strongly correlated with disease severity [4] .

With our data and using classical RT-PCR, we observed that especially immunosuppressed critically ill patients tended to be viremic with SARS-CoV-2. In contrast to Veyer et al., we did not observe any association with mortality. Further larger multicentric cohorts are urgently needed to investigate risk factors for RNAemia using classical and ultrasensitive RT-PCR methods in severe and non-severe COVID-19 patients. M a n u s c r i p t M a n u s c r i p t 8 Legend. *Adjustment for the time interval between onset of symptoms and date of sampling. OR: Odds ratio. CI: Confidence interval. SOFA: Sequential organ failure assessment score. ICU: Intensive care unit. A sensitivity analysis forcing the variables "SOFA" and "chronic respiratory failure" in the multivariable analysis showed similar results (OR for immunosuppression 8.35, 95% CI 0.89-78.29, p=0.063).

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely correlated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients

Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity. Emerging microbes & infections 2020

Highly sensitive quantification of plasma SARS-CoV-2 RNA shelds light on its potential clinical value. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

Evaluation of the RealStar(R) SARS-CoV-2 RT-PCR kit RUO performances and limit of detection

A c c e p t e d M a n u s c r i p t 6 A c c e p t e d M a n u s c r i p t